Breath Analyte Detection Device

ABSTRACT

A breath analyte device includes a breath volume in fluid communication with a sampling volume. The device also includes a sampling sensor configured to generate a breath signal that varies in response to changes in gas pressure (e.g., sound waves) in the breath volume and an analyte sensor configured to generate an analyte signal that varies in response to a concentration of a target analyte present in the sampling volume. A control unit is configured to determine a time at which to measure the concentration of the target analyte in the sampling volume based on the breath signal and measure the concentration of the target analyte in the sampling volume based on the analyte signal at the determined time. The device may also include a pump configured to motivate gas from the breath volume into the sampling volume prior to measuring the concentration of the target analyte.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/695,882, filed Jul. 10, 2019, which is incorporated by reference.

BACKGROUND 1. Technical Field

The subject matter described relates generally to chemical detectionand, in particular, to devices that detect specific analytes in exhaledbreath.

2. Background Information

Exhaled breath contains many analytes that are non-invasive indicatorsof various physiological conditions. Because breath may be monitorednon-invasively, breath acetone measurement is attractive as a tool formonitoring lifestyle modifications that impact health such as dietaryadherence and weight-loss. For example, breath acetone correlates withmetabolic status in humans and can be used to quantify adherence to areduced carbohydrate/calorie diet, exercise and, for diabetics,progression towards a life-threatening condition called ketoacidosis.

To this end, multiple entities have attempted to produce breath acetoneproducts that consumers can use at home to measure and track breathacetone. However, existing approaches suffer from deficiencies thatreduce the accuracy and reproducibility of the breath acetonemeasurement. Furthermore, existing approaches generally struggle todistinguish between acetone and other analytes in human breath.Consequently, the value of existing solutions (both commercially and inproviding health benefits) is limited.

SUMMARY

A breath analyte device uses a sampling sensor to determine when tosample a user's breath for detection of a target analyte. A sample ofthe user's breath is drawn into a sampling volume (e.g., a flow cell)that includes an analyte sensor at the determined time. The analytesensor may be chosen based on its response to the target analytes andother analytes typically present in breath. The device includes acontrol unit configured to determine the amount of the target analytepresent in the user's breath using the output from the analyte sensor.

In various embodiments, the sampling sensor is an audio sensor (e.g., amicrophone). The device samples the user's alveolar breath byidentifying the end portion of the user's breath from the output fromthe audio sensor. The control unit may identify the beginning of abreath by an increase in the output from the audio sensor relative to abase level. The output from the audio sensor will typically increase toa peak value and then begin to decrease through the breath. The endportion of the breath may begin when the output from the audio sensordrops below a threshold defined relative to the peak value and end whenthe output returns to the base level. Sampling alveolar breath may bereferred to as “end-of-breath” or “late-breath” sampling.

In one embodiment, a breath analyte device detects the presence andconcentration of acetone in a user's breath. The device includes abreath volume for receiving gas exhaled from a user and a flow cell influid communication with the breath volume. A microphone is in fluidcommunication with the breath volume and an acetone sensor is in fluidcommunication with the flow cell. The acetone sensor may be selected toprovide a good signal-to-noise ratio in its response to acetone versushydrogen and other breath analytes. A control unit detects the approachof the end of the user's breath from audio data generated by themicrophone and activates a pump to move a portion of the user's breathfrom the breath volume to the flow cell. The control unit then generatesa measurement of the amount of acetone in the user's breath from theoutput of the acetone sensor.

The acetone sensor may be refreshed between each measurement to improveconsistency and accuracy. For example, when the breath acetone device isturned on or woken up, the flow cell may be cleared by the pump and theacetone sensor heated to an elevated temperature to burn off adsorbedchemicals and generate negatively charged oxygen species at the activesurface. The pump may be activated again (or it may remain on) to removedesorbed chemicals from the flow cell and the acetone sensor ismaintained at an elevated temperature sufficient to prevent significantadsorption of chemicals. In response to user input requesting ameasurement, the temperature of the acetone sensor is reduced to asampling temperature.

The combination of end-of-breath sampling and analyte sensor selectionmay provide high accuracy breath acetone measurements without the needfor complex, bulky, or expensive equipment. Consequently, the breathanalyte device may be handheld and operated by users without specializedmedical training. The device may also be relatively low-cost, making itattractive for a wide range of applications, from monitoring potentiallylife-threatening diseases to encouraging adherence to fitness programs.The breath analyte device is also non-invasive, making it preferable tousers over other diagnostic techniques, such as blood tests.

BRIEF DESCRIPTION OF THE DRAWINGS

The figures and following description describe certain embodiments byway of illustration only. One skilled in the art will readily recognizefrom the following description that alternative embodiments of thestructures and methods may be employed without departing from theprinciples described. Wherever practicable, similar or like referencenumbers are used in the figures to indicate similar or likefunctionality.

FIG. 1 is a schematic diagram of a breath acetone device, according toone embodiment.

FIG. 2 is perspective view of the exterior housing of the breath acetonedevice of FIG. 1, according to one embodiment.

FIG. 3 is perspective view of the interior of the breath acetone deviceof FIG. 1, according to one embodiment.

FIG. 4 is a block diagram illustrating a computer-based control unit ofa breath acetone measurement device, according to one embodiment.

FIG. 5 is a flowchart illustrating a method of sampling a user's breath,according to one embodiment.

FIG. 6 is a graph illustrating the use of the output of an audio sensorfor end-of-breath sampling, according to one embodiment.

FIG. 7 is a flowchart illustrating end-of-breath threshold 630,according to one embodiment.

DETAILED DESCRIPTION

The accurate and reproducible measurement of breath analytes has severalchallenges. These challenges include sample timing, sensor sensitivity,analyte differentiation. These challenges are particularly pertinent forhandheld or otherwise portable devices intended for use by individualswithout specialized training. Portability places restraints on the sizeand weight of components that may be used as well as the extent to whichtesting conditions can be controlled. Similarly, operation by untrainedusers limits the extent to which test conditions can be controlled andmanaged. Commercial concerns may also place limits on the componentsused.

With regard to sample timing, the concentrations of analytes in a humanbreath vary according to the depth of exhalation. Thus, accuracy andreproducibility of breath analyte measurement can be improved byconsistently sampling from the portion of the breath cycle with a highrelative concentration of the target analyte. For example, in the caseof acetone, the beginning of a breath contains the lowest concentrationdue to dilution with outside air and the end of the breath contains thehighest concentration due to the highest degree of transfer from theblood in the lungs and airways. Therefore, end-of-breath sampling mayprovide improved accuracy and reproducibility.

With regard to sensor sensitivity, the concentration of breath analytescan vary over a relatively large range. For example, acetone can rangefrom ˜100 parts per billion (ppb) to >100 parts per million (ppm). Theresponse of the analyte sensor to the target analyte throughout therange that it is likely to appear in human breath can significantlyimpact accuracy and reproducibility.

With regard to analyte differentiation, human breath contains a varietyof chemical analytes. Typically, sensors are sensitive to severalanalytes in human breath. For example, many acetone sensors also respondto hydrogen, carbon monoxide, alcohols, isoprene, and/or ammonia.Different sensors have different ratios of sensitivity between acetoneand these other analytes. Thus, accounting for expected sensor responsesdue to other analytes may significantly improve the accuracy andreproducibility of measurements of target analytes.

In the description that follows, various principles are described withreference to an example breath acetone device for convenience. Thisshould not be taken as limiting the scope of this disclosure to suchdevices. Rather, it should be understood that many of these principlesare applicable to breath analyte devices configured to detect otheranalytes.

Example Breath Acetone Device

FIG. 1 illustrates one embodiment of a breath acetone device 100. In theembodiment shown, the device 100 includes a breath volume 110, a flowcell 120, a pump 130, an acetone sensor 140, a sampling sensor 150, anda control unit 160, all within a housing 170. The breath volume 110 isfluidly connected to the exterior environment by an input aperture 101in the housing (e.g., a mouthpiece) and an output aperture 102 (e.g., avent or valve). The breath volume 110 is fluidly connected to the flowcell 120 via a flow conduit 112. The sampling sensor 150 is fluidlyconnected to the breath volume 110 via a sampling conduit 115. The pump130 is fluidly connected to the flow cell 120 via a pump conduit 123.The pump 130 may also be fluidly connected to the exterior environmentby a vent 135. In other embodiments, the breath acetone device 100 mayinclude different or additional elements.

The breath volume 110 generally forms a conduit through which airexhaled by a user may pass through. A user may press their lips aroundthe input aperture 101 and exhale into the breath volume. The exhaledair may then freely or with restriction pass from the input aperture101, through the breath volume 110, and out of the output aperture 102.The breath volume 110 may be configured in any shape and size. Forexample, the breath volume 110 may comprise a generally cylindricalshape, rectangular prism shape, or any other shape. Preferably, a breathvolume 110 is made from a substantially rigid and/or flexible materialor combination of materials. In various embodiments, the breath volume110 has a volume of approximately 5 to 200 milliliters, although largerand smaller sizes may be used.

The flow cell 120 includes a chamber or conduit configured for directinggas towards and away from an acetone sensor 140. The flow cell 120 maybe configured in any size and shape and may preferably be made from asubstantially rigid and/or flexible material or combination ofmaterials. In various embodiments, the flow cell 120 has a volume ofapproximately 2 to 200 milliliters, such as 2 to 50 milliliters,although larger and smaller sizes may be used. In the embodiment shownin FIG. 1, the flow cell 120 is in fluid communication with the breathvolume 110 via a flow conduit 112. The flow conduit 112 is a passageway,such as a tube, that allows gas to flow between the breath volume 110and flow cell 120. In other embodiments, the flow cell 120 may becoupled to the breath volume 110 in other ways.

The sampling sensor 150 gathers data that the control unit 160 can useto determine an appropriate time to sample the user's breath. Thesampling sensor 150 outputs a sampling signal that varies in response toone or more variables that are indicative of the stage of the user'sbreath. In various embodiments, the sampling sensor 150 is an audiosensor that detects perturbations in gas pressure in the vicinity of thedevice 100 (e.g., in the breath volume 110) that are indicative of theapproach of the end of a user's breath. In the embodiment shown in FIG.1, the audio sensor 150 is in fluid communication with the breath volume110 via the sampling conduit 115. The sampling conduit 115 is apassageway, such as a tube, that allows gas to flow between the breathvolume 110 and the audio sensor 150.

In one embodiment, the audio sensor 150 is a microphone configured topick up or record audio information. The microphone may include anyacoustic-to-electric transducer or sensor that converts sound waves inthe surrounding gas into an electrical signal that it provides to thecontrol unit 160. Example types of microphone include electromagneticinduction microphones (dynamic microphones), capacitance changemicrophones (condenser microphones), and piezoelectricity microphones(piezoelectric microphones). The output from the microphone may bepassed through one or more frequency filters to remove components of theaudio spectrum that do not correlate strongly with the approach of theend of the user's breath. For example, a high pass filter may be appliedto remove frequencies below approximately one kilohertz (kHz) and/or alow pass filter may be applied to remove above approximately ten kHz.

In alternative embodiments, the sampling sensor 150 may comprise apressure sensor a which may be configured to record air pressureinformation from the environment around the device 100 and/or within thebreath volume 110. Example pressure-type sampling sensors 150 includesilicon MEMS strain gauge sensors, piezoresistive silicon pressuresensors, analog output pressure transducer sensors, remote wirelesspressure transducers, harsh media pressure sensors, digital outputabsolute pressure sensors, IsoSensor pressure sensors, solid statepressure sensors, or any other type of air pressure sensing method ordevice.

The pump 130 is configured to motivate air between the breath volume 110and the flow cell 120. The pump 130 may include any device configured tocause, motivate, or direct air flow. Example pumps 130 include arotating arrangement of vanes or blades capable of moving air, such as arotary vane pump, a diaphragm pump, a piston pump, a scroll pump, ascrew pump, a Wankel pump, an external vane pump, a roots blower orbooster pump, a multistage roots pump, a blower fan, a vane pump,axial-flow fans, centrifugal fans, cross-flow fans, bellows, Coandăeffect air movers, electrostatic air movers, or any other device ormethod capable of moving air.

In various embodiments, when the output from the audio sensor 150indicates the end of the user's breath is approaching, the control unit160 activates the pump such that a portion of the user's breath ispumped from the breath volume 110 to the flow cell 120. In theembodiment shown in FIG. 1, the pump 130 pulls gas out of the flow cell120 via the pump conduit 123, which is a passageway, such as a tube,that allows air to flow between the pump 130 and flow cell 120. Theremoval of gas results in a negative pressure differential between theflow cell 120 and the breath volume 110. Consequently, gas (e.g., theuser's breath) moves from the breath volume 110 into the flow cell 120.In other embodiments, the pump 130 may create or generate an increase inpressure in the flow cell 120 which may cause gas within the flow cell120 to be replaced by gas from outside of the flow cell 120 (e.g., freshair).

In embodiments that include a vent 135 in fluid communication with apump 130, the vent 135 may provide a source of fresh air for the pump130 to provide or exchange with the flow cell 120. The vent 135 is apassageway, such as a tube, which allows air to flow into and/or out ofthe pump 130. For example, for pumps 130 that only pull (as opposed topull and also push), the vent 135 may be used as a source of fresh airwith which to clear the flow cell 120 after a breath measurement toprepare the device 100 for the next measurement. Alternatively, a pump130 that can both push and pull may be used. In this case, the pump 130first pulls the breath sample into the flow cell 120 and then, after themeasurement, pushes the breath sample back into the breath volume 110.Thus, the vent 135 may be omitted.

The acetone sensor 140 generates an output acetone signal that varieswith the concentration of acetone in gas to which it is exposed. Forexample, the output may be an electrical signal that increases withacetone concentration at an active surface of the sensor 140. In oneembodiment, the acetone sensor 140 includes a metal-oxide sensor, suchas a tungsten oxide or zinc oxide sensor (e.g., the SB-33 or SP-33sensors provided by Nissha FIS). The metal oxide sensor may includeadditional metal oxides. For example, a tungsten oxide sensor may bedoped with gold, platinum, iron, silicon, gadolinium, holmium, yttriumand/or other rare earth materials.

The acetone sensor 140 may be selected to be significantly moreresponsive to acetone than other analytes that may be present in breath.In some embodiments, the acetone sensor 140 is at least fifty times moresensitive to acetone than one or more of: hydrogen, alcohols, carbonmonoxide, ammonia, methane, or other chemicals commonly found in exhaledbreath. In other embodiments, the acetone sensor 140 is at least twentytimes more sensitive to acetone than one or more of: hydrogen, alcohols,carbon monoxide, ammonia, methane, or other chemicals commonly found inexhaled breath.

The control unit 160 is a computing device configured to controloperation of and/or receive data from other components of the breathacetone device 100. In one embodiment, the control unit 160 is coupled(e.g., optically or electrically) to the pump 130 and controls itsoperation. The control unit 160 is also coupled (e.g., optically orelectrically) to the acetone sensor 140 and audio sensor 150. Thecontrol unit 160 receives and processes data from the acetone sensor 140and audio sensor 150. The control unit 60 may also control one or moreI/O interfaces of the device 100. Various embodiments of the controlunit 160 are described in greater detail below, with reference to FIG.4.

FIG. 2 illustrates the exterior of the example breath acetone device 100shown in FIG. 1. The housing 170 may be configured in any shape andsize, such as an ovoid shape, rectangular prism shape, triangular prismshape, or any other shape. In one embodiment, the housing has a maximumlength between five and twenty centimeters, a maximum width between twoand ten centimeters, and a maximum depth between one and threecentimeters. Thus, the breath acetone device 100 may be handheld andeasily stored in a user's pocket or bag.

In some embodiments, a housing 170 may be made from or may comprise asubstantially rigid material, such as steel alloys, aluminum, aluminumalloys, copper alloys, other types of metal or metal alloys, ceramicssuch as alumina, porcelain, and boron carbide, earthenware, naturalstone, synthetic stone, various types of hard plastics, such aspolyethylene (PE), Ultra-high-molecular-weight polyethylene (UHMWPE,UHMW), polypropylene (PP) and polyvinyl chloride (PVC), polycarbonate,nylon, Poly(methyl methacrylate) (PMMA) also known as acrylic, melamine,hard rubbers, fiberglass, carbon fiber, resins, such as epoxy resin,wood, other plant based materials, or any other material includingcombinations of materials that are substantially rigid. In furtherembodiments, a housing 170 may be made from or may comprise a flexiblematerial such as natural and/or synthetic rubber material such as latexrubber, forms of the organic compound isoprene, Polyacrylate Rubber,Ethylene-acrylate Rubber, Polyester Urethane, flexible plastics, such ashigh-density polyethylene (HDPE), polyvinyl chloride (PVC),polypropylene (PP), Polystyrene (PS), Polycarbonate (PC), low densitypolyethylene (LDPE), or any other flexible material includingcombinations of materials.

The device 100 may include one or more I/O interfaces on the exterior ofthe housing 170. In the embodiment shown in FIG. 2, the device 100 has adisplay 210, an action button 220, a menu button 230, and a UniversalSerial Bus (USB) port 240. The display 210 presents information such asinstructions and results to users. The action button 220 may transitionthe device from an off (or sleeping) state to an on (or ready) states,initiate a measurement, and/or select menu options (e.g., an optioncurrently highlighted on the display 210). The menu button 230 mayenable user-selection if various options (e.g., pressing the menu button230 a first time may cause a menu to be displayed on the display 210with a first option highlighted and pressing it additional times maycycle through highlighting of additional options). The USB port 240provides an interface via which data can be uploaded to and downloadedfrom the device 100. For example, breath acetone measurements may bedownloaded to a computer for aggregation and analysis and softwareupdates may be uploaded to the device 100. In other embodiments, thedevice 100 may include different or additional I/O interfaces.Furthermore, the functionality may be distributed between I/O interfacesin a different manner than described.

FIG. 3 illustrates the interior of the example breath acetone device 100shown in FIG. 1. In the embodiment shown in FIG. 3, the flow cell 120,pump 130, acetone sensor 140, and sampling sensor 150 are mounted on aprinted circuit board of the control unit 160. This configuration may beconvenient for manufacture as it makes coupling the control 60 to theother components (e.g., electrically) relatively straight forward. Thecompact arrangement also enables the breath acetone device 100 to berelatively small to conveniently fit in a user's hand, pocket, bag, etc.

Example Control Unit

FIG. 4 illustrates one embodiment of the control unit 160 of a breathacetone device 100. In the embodiment shown in FIG. 4, the control unit160 includes a processor 410, I/O interfaces 420, a wireless interface430, data store 440, and a memory 450. The memory 450 includes anoperating system (OS) 460 and one or more programs 470. It should beappreciated that FIG. 4 depicts an example of a control unit 160 in anoversimplified manner, and a practical embodiment may include additionalcomponents or elements and suitably configured processing logic tosupport known or conventional operating features that are not describedin detail herein.

The components of a control unit 160 and other elements of the breathacetone device 100 (e.g., the pump 130, acetone sensor 140, and audiosensor 150) may be communicatively coupled via a local interface 480.The local interface 480 can be, for example, one or more buses or otherwired or wireless connections, integrated circuits, etc. The localinterface 480 can have additional elements, which are omitted forsimplicity, such as controllers, buffers (caches), drivers, repeaters,and receivers, among many others, to enable communications. Further, thelocal interface 480 may include address, control, and/or dataconnections to enable appropriate communications among the othercomponents.

The processor 410 is one or more hardware devices for executing softwareinstructions. The processor 410 can be any custom made or commerciallyavailable processor, such as a central processing unit (CPU), anauxiliary processor among several processors, a semiconductor-basedmicroprocessor (in the form of a microchip or chip set), or generallyany device for executing software instructions. When in operation, theprocessor 410 is configured to execute software stored within the memory450, to communicate data to and from the memory 450, and otherwisecontrol operations of the device 100 pursuant to the softwareinstructions. In one embodiment, the processor 410 is optimized for usein a handheld device. For example, the processor 410 may be configuredfor low power consumption.

The I/O interfaces 420 can be used to input and/or output informationand/or power to the device 100. In some embodiments, the I/O interfaces420 may include one or more input interfaces, including turnable controlknobs, depressible button type switches, key pads, slide type switches,dip switches, rocker type switches, rotary dial switches, numeric inputswitches, or any other suitable input which a user may interact with toprovide input. The I/O interfaces 420 may also include one or moreinformation displays, including light emitting diode (LED) displays, LCDdisplays, speakers, or any other suitable devices for outputting ordisplaying information. The I/O interfaces 420 can also include one ormore data output ports, including USB ports, serial ports, parallelports, small computer system interface (SCSI) ports, and the like.Example I/O interfaces include the display 210, action button 220, menubutton 230, and USB port 240 shown in FIG. 2. In one embodiment, thebreath acetone device 100 includes rechargeable power source (e.g., abattery or capacitor) and an I/O interface 420 (e.g., the USB port 240)may be used to charge the power source.

The wireless interface 430 (if included) enables wireless communicationto an external access device or network. The wireless interface 430 mayinclude a wireless communication receiver and/or a wirelesscommunication transmitter. In one embodiment, the wireless interface 430operates on a cellular band and may communicate with or receive aSubscriber Identity Module (SIM) card or other wireless networkidentifier. In other embodiments, other wireless data communicationprotocols, techniques, or methodologies may be used, including: radiofrequency (RF) transmissions; IrDA (infrared); Bluetooth; ZigBee (andother variants of the IEEE 802.15 protocol); IEEE 802.11 (e.g., WiFi);IEEE 802.16 (WiMAX or any other variation); Direct Sequence SpreadSpectrum; Near-Field Communication (NFC); Frequency Hopping SpreadSpectrum; Long Term Evolution (LTE); cellular/wireless/cordlesstelecommunication protocols (e.g. 3G/4G, etc.); wireless home networkcommunication protocols; paging network protocols; magnetic induction;satellite data communication protocols; wireless hospital or health carefacility network protocols such as those operating in the WMTS bands;GPRS; proprietary wireless data communication protocols such as variantsof Wireless USB; or any other suitable protocols, techniques, ormethodologies for wireless communication.

The data store 440 is configured to store data generated and/or used bythe breath acetone device 100. For example, the data store 440 mayinclude breath acetone measurements made by the device 100. The datastore 440 may include any of volatile memory elements (e.g., randomaccess memory (RAM, such as DRAM, SRAM, SDRAM, and the like)),nonvolatile memory elements (e.g., ROM, hard drive, tape, CDROM, and thelike), and combinations thereof. Moreover, the data store 440 mayincorporate electronic, magnetic, optical, and/or other types of storagemedia.

The memory 450 may include any of: volatile memory elements (e.g.,random access memory (RAM, such as DRAM, SRAM, SDRAM, etc.)),nonvolatile memory elements (e.g., ROM, hard drive, etc.), andcombinations thereof. Moreover, the memory 450 may incorporateelectronic, magnetic, optical, and/or other types of storage media. Notethat the memory 450 may have a distributed architecture, where variouscomponents are situated remotely from one another, but can be accessedby the processor 410. The software in memory 450 can include one or moresoftware programs, each of which includes an ordered listing ofexecutable instructions for implementing logical functions.

In the example of FIG. 4, the software in the memory 450 includes anoperating system (O/S) 460 and programs 470. The operating system 460controls the execution of input/output interfaces 420 and providesscheduling, file and data management, memory management, communicationcontrol, and related services. The operating system 460 may be, forexample, LINUX (or another UNIX variant) and any Linux-kernel-basedoperating systems, Raspbian, Ubuntu, OpenELEC, RISC OS, Arch Linux ARM,OSMC (formerly Raspbmc) and the Kodi open source digital media center,Pidora (Fedora Remix), Puppy Linux, Android (available from Google),Symbian OS, Microsoft Windows CE, Microsoft Windows 7 Mobile, iOS(available from Apple, Inc.), webOS (available from Hewlett Packard),Blackberry OS (Available from Research in Motion), and the like. Theprograms 470 may include various applications, add-ons, etc. configuredto provide end user functionality such as customized control of one ormore pumps 130, acetone sensors 140, and/or sampling sensors 150.

Example Methods

FIG. 5 illustrates a method 500 for sampling a user's breath, accordingto one embodiment. The steps of FIG. 5 are illustrated from theperspective of various components of the breath acetone device 100performing the method 500. However, some or all of the steps may beperformed by other entities or components. In addition, some embodimentsmay perform the steps in parallel, perform the steps in differentorders, or perform different steps.

In the embodiment shown in FIG. 5, the method 500 begins with receiving510 user input activating the device 100. For example, the user maybegin the process by pressing the action button 220 to turn on or wakeup the device 100. The control unit 160 prepares 520 the acetone sensor140 to take a measurement. This may include refreshing the sensor 140(e.g., by heating it to an elevated temperature) and/or heating it toits operating temperature. An example process for preparing 520 anacetone sensor 140 is described in greater detail below, with referenceto FIG. 7.

Once the sensor 140 is ready, the control unit 160 obtains 530 abaseline reading from the sensor and prompts 540 the user to blowthrough the breath volume 110 (e.g., via an I/O interface 420 using agraphic, vibration, sound, or other indicator). The baseline may be adynamic baseline (e.g., determined by averaging the sensor response overa two second period). The control unit 160 identifies 550 theapproaching end of breath of the user based on the output from the audiosensor 150. An example approach to identifying 550 the approaching endof breath of the user is described in greater detail below, withreference to FIG. 6.

Regardless of how the approaching end of breath is identified, thedevice 100 collects 560 a breath sample (e.g., by activating the pump130 to pull the sample from the breath volume 110 into the flow cell120). The control unit 160 determines 570 the acetone level in thebreath sample based on the output from the acetone sensor 140. Forexample, the control unit 160 may integrate the response of the acetonesensor 140 to the breath sample over a sample period and subtract thebaseline level. The control unit 160 may also apply a drift correctionterm that accounts for changes in sensor behavior over time (e.g., dueto wear and tear, etc.). The drift correction term may be calculatedduring calibration. In some embodiments, the acetone sensor 140 operatesin a pulsed heating mode. This may provide additional information (e.g.,to distinguish between sensor response due to acetone and distractorssuch as hydrogen).

The measurement may be presented 580 to the user (e.g., using a displayI/O interface 420) and/or stored for later output (e.g., in the datastore 440). Once the analyte level has been determined 570, the pump 130may reactivate to clear the flow cell 120 and/or the control unit 160may prepare 520 the acetone sensor 140 for another measurement.

FIG. 6 illustrates an example approach that uses an audio sensor 150 todetect the approaching end of a user's breath. As a user blows a fullbreath through the breath volume 110, the output of the audio sensor 150first rises and then falls. When the signal stops rising and startsdecreasing again, this indicates that the user is getting close to theend-of-breath. Note that the average pressure within the breath volume110 behaves similarly throughout a breath cycle.

In one embodiment, the control unit determines that a full breath isoccurring when the output from the audio sensor 150 increases above abreath-detection threshold 610. The breath-detection threshold 610 maybe set at a level such that ambient noise is unlikely to exceed it. Oncethe output increases above the breath-detection threshold 610, thecontrol unit 160 monitors the output to identify the maximum 620. Themaximum 620 may be identified by the output from the sensor consistentlydecreasing for a predetermined period (e.g., 0.1 seconds) and/ordecreasing by more than a threshold amount (e.g., 90% of the previouslyobserved maximum).

Once the output drops below an end-of-breath threshold 630, the controlunit 160 may trigger sampling of the user's breath (e.g., by activatingthe pump to pull a portion of the user's breath into the flow cell 120and thus into contact with the acetone sensor 140). The end-of-breaththreshold 630 may be set to any proportion of the maximum 620. In oneembodiment, the end-of-breath threshold 630 is in the range from 75-98%of the maximum 620. In other embodiments, other end-of-breath thresholds630 may be used

FIG. 7 illustrates a method for preparing 520 a metal-oxide sensor(e.g., acetone sensor 140) for sampling, according to one embodiment.Metal oxide sensors (MOS) are composed of a catalytic metal-oxide coatedonto a heating element. Heating the metal-oxide to high temperatures(e.g., 200-400C) yields negatively charged oxygen species adsorbed atthe metal-oxide active surface. These surface ions react with ambienttarget gases and release electrons into the metal-oxide film resultingin a change of electrical resistivity of the metal-oxide layer. Thus,the change of resistivity measured between two electrodes on the sensor140 directly depends on the ambient target gas concentration. However,this is an inherently unstable system. The method shown in FIG. 7 canimprove reliability and reproducibility of results by refreshing thesensor before a measurement is taken. The steps of FIG. 7 areillustrated from the perspective of various components of the breathacetone device 100 performing the method. However, some or all of thesteps may be performed by other entities or components. In addition,some embodiments may perform the steps in parallel, perform the steps indifferent orders, or perform different steps.

In the embodiment shown in FIG. 7, the method begins by activating 710the pump 130 to clear the flow cell 120. The control unit 160 heats 720the sensor to a first temperature to burn off any adsorbed chemicals andgenerate negatively charged oxygen species at the active surface of thesensor 140. For example, the first temperature may be between 200 C and500 C. The control unit 160 may activate 730 the pump 130 again (or itmay remain pumping after step 710) to remove desorbed chemicals from theflow cell 120.

The control unit 160 holds 740 the sensor 140 at a second temperaturethat is sufficient to prevent significant adsorption of chemicals at theactive surface. The second temperature may be the same or lower than thefirst temperature. For example, the second temperature may be between150 C and 350 C. At this point, the control unit 160 may inform the userthat the device 100 is ready to take a measurement (e.g., with a prompton the display 210). If the device 100 remains in this state for morethan a predetermined amount of time, the control unit 160 may abort themeasurement and return the device 100 to a sleeping or off state. Thisprevents excessive battery use and potential damage to the device 100that may arise from maintaining the sensor 140 at an elevatedtemperature.

Assuming the control unit 160 receives 760 user input requesting ameasurement (e.g., the user pressing the action button 220), thetemperature of the sensor 140 is adjusted 760 to a third temperature.The third temperature may be selected to optimize the response of thesensor 140 to acetone. For example, the third temperature may be between200 C and 400 C. Once the sensor 140 reaches the third temperature, thedevice 100 may proceed with sampling the user's breath (e.g., asdescribed previously with reference to FIG. 5).

Example Devices for Measuring Other Breath Analytes

As noted previously, while the above description focuses on measuringbreath acetone, similar devices may be manufactured to detect otheranalytes in breath for various purposes. For example, Carbon monoxide(CO) is elevated in the exhaled breath of smokers and the concentrationof CO can serve as a marker of smoking and smoking cessation. Similar toacetone, CO increases with the depth of an exhalation reaching anapproximate steady-state close to the end-of-breath. In one embodiment,a breath CO device uses an electrochemical or fuel-cell sensor. Ratherthan use a heated catalytic element to oxidize the breath analyte asdone by metal-oxide sensors, electrochemical sensors utilize a voltagebias between a catalytic or “working” electrode and a counter electrodeto oxidize or reduce the gas analyte. A third electrode may be used inelectrochemical CO sensors to maintain a substantially constant bias atthe working electrode keeping the reaction rate and sensitivity of thesensor to CO constant. Many two- and three-electrode CO sensors may beused, including the NAP-505 and NAP-508 sensors from Nemoto, theEC4-500-CO sensor from SGX, and the FECS40-1000 sensor from Figaro.

One limitation of three-electrode CO sensors is a cross sensitivity tohydrogen which can be elevated in breath and make accurate measurementsof CO in breath difficult. Therefore, in some embodiments, a CO breathdevice includes a four-electrode electrochemical sensor to reducecross-sensitivity to hydrogen, such as the CO/CF-200-4E from Membraporand the A3E/F from City Technology. These four-electrode sensors includean additional catalytic electrode that is sensitive to hydrogen but notCO, thus enabling the device to correct for the presence of hydrogen inthe sample.

As another example, Hydrogen (H2) and methane (CH4) are generated bymicrobial fermentation of carbohydrates in the human bowel. This occurswhen dietary carbohydrates are not absorbed in the small intestine andtravel along the digestive tract into the large intestine. The generatedhydrogen and methane are absorbed into the blood and subsequentlyemitted in the breath. The only source of hydrogen and methane in thebreath is due to this mechanism. Because of this, hydrogen/methanebreath tests can be used to detect carbohydrate maladsorption syndromessuch as lactose, sucrose and/or fructose intolerance as well asdiagnosing bacterial overgrowth of the small bowel (SIBO), a conditionin which larger-than-normal numbers of colonic bacteria are present inthe small intestine.

In one embodiment, a hydrogen/methane breath device includes a metaloxide sensor that shows selectivity to these gasses, such as the TGS821,TGS2611-000, and TGS2611-E00 from Figaro and the SB-11A, 12A, and 12Cfrom Nissha FIS. The device may also include a catalytic filter in frontof the sensor to reduce the response to interfering analytes in breath.In another embodiment, the hydrogen/methane breath device includes anelectrochemical sensor that can be used to measure H2 in breath, such asthe 4YHT from City Technology and the H2/M-1000, H2/CA-1000, andH2/C-2000 from Membrapor. Another method of detecting methane in breathuses NDIR sensors which use infrared light absorption to selectivelydetect hydrocarbons in breath, such as the IR12BD from SGX.

As a further example, breath ammonia concentration is correlated withthe presence of nitrogenous wastes such as urea in blood and thereforemay be used as a method for monitoring hemodialysis and kidney functionin patients with kidney disease. In one embodiment, a breath ammoniadevice includes a metal-oxide sensor, such as the TGS826 from Figaro andthe MIC-5914 from SGX. In another embodiment, the breath ammonia deviceincludes an electrochemical sensor, such as the SGX-4NH3 from SGX andthe FECS44-100 from Figaro. One advantage of these electrochemicalsensors is their inherent insensitivity to interferents in breath suchas hydrogen and ethanol.

One of skill in the art will appreciate that detection devices may beconstructed for other breath analytes by selecting an appropriatesensor. For example, using the principles disclosed, one could constructa breath measurement device for volatile sulfur compounds, isoprene,trimethylamine, or the like.

ADDITIONAL CONSIDERATIONS

Some portions of above description describe the embodiments in terms ofalgorithmic processes or operations. These operations, while describedfunctionally, computationally, or logically, are understood to beimplemented by computer programs including instructions for execution bya processor or equivalent electrical circuits, microcode, or the like.

As used herein, any reference to “one embodiment” or “an embodiment”means that a particular element, feature, structure, or characteristicdescribed in connection with the embodiment is included in at least oneembodiment. The appearances of the phrase “in one embodiment” in variousplaces in the specification are not necessarily all referring to thesame embodiment.

Some embodiments may be described using the expression “coupled” and“connected” along with their derivatives. It should be understood thatthese terms are not intended as synonyms for each other. For example,some embodiments may be described using the term “connected” to indicatethat two or more elements are in direct physical or electrical contactwith each other. In another example, some embodiments may be describedusing the term “coupled” to indicate that two or more elements are indirect physical or electrical contact. The term “coupled,” however, mayalso mean that two or more elements are not in direct contact with eachother, but yet still co-operate or interact with each other. Theembodiments are not limited in this context.

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “has,” “having” or any other variation thereof, areintended to cover a non-exclusive inclusion. For example, a process,method, article, or apparatus that comprises a list of elements is notnecessarily limited to only those elements but may include otherelements not expressly listed or inherent to such process, method,article, or apparatus. Further, unless expressly stated to the contrary,“or” refers to an inclusive or and not to an exclusive or. For example,a condition A or B is satisfied by any one of the following: A is true(or present) and B is false (or not present), A is false (or notpresent) and B is true (or present), and both A and B are true (orpresent).

In addition, use of the “a” or “an” are employed to describe elementsand components of the embodiments. This is done merely for convenienceand to give a general sense of the disclosure. This description shouldbe read to include one or at least one and the singular also includesthe plural unless it is obvious that it is meant otherwise. Furthermore,where values are described as “approximate” or “substantially” (or theirderivatives), such values should be construed as accurate+/−10% unlessanother meaning is apparent from the context. From example,“approximately ten” should be understood to mean “in a range from nineto eleven.”

Upon reading this disclosure, those of skill in the art will appreciatestill additional alternative structural and functional designs for asystem and a process for measuring breath analyte levels. Thus, whileparticular embodiments and applications have been illustrated anddescribed, it is to be understood that the described subject matter isnot limited to the precise construction and components disclosed hereinand that various modifications, changes and variations which will beapparent to those skilled in the art may be made in the arrangement,operation and details of the method and apparatus disclosed. The scopeof protection should be limited only by the following claims.

What is claimed is:
 1. A method for measuring concentration of a breathanalyte, the method comprising: receiving gas exhaled by a user in abreath volume; receiving, from a sampling sensor, a breath signal thatvaries in response to changes in gas pressure in the breath volumeidentifying a sample time based on the breath signal; receiving, from ananalyte sensor, an analyte signal that varies in response to aconcentration of the breath analyte present in a sampling volume; andmeasuring the concentration of the breath analyte in the sampling volumebased on the analyte signal.
 2. The method of claim 1, whereinidentifying the sample time comprises: detecting the breath signalincreasing above a breath-detection threshold; identifying a maximum inthe breath signal after the breath signal increased above thebreath-detection threshold; and detecting the breath signal droppingbelow an end-of-breath threshold after the maximum in the breath signal,wherein the sample time is when the breath signal drops below theend-of-breath threshold.
 3. The method of claim 1, further comprisingpumping a portion of the gas exhaled by the user from the breath volumeto the sample volume prior to measuring the concentration of the breathanalyte in the sampling volume.
 4. The method of claim 1, whereinmeasuring the concentration of the breath analyte in the sampling volumecomprises: integrating the analyte signal over a sample period; andsubtracting, from the integrated analyte signal, one or more of abaseline level or a drift correction.
 5. The method of claim 1, furthercomprising preparing the analyte sensor for sampling by: heating theanalyte sensor to a first temperature sufficient to burn off at leastsome chemicals adsorbed on an active surface of the analyte sensor;holding the analyte sensor at a second temperature sufficient to preventsignificant adsorption of chemicals at the active surface; receiving asignal indicating a request to measure the analyte concentration usingthe analyte sensor; and adjusting the temperature of the analyte sensorto a third temperature, wherein the analyte sensor is configured tomeasure the analyte concentration while the analyte sensor is at thethird temperature.
 6. A breath analyte device comprising: a breathvolume; a sampling volume in fluid communication with the breath volume;a sampling sensor located in or adjacent to the breath volume andconfigured to generate a breath signal that varies in response tochanges in gas pressure in the breath volume; an analyte sensor in fluidcommunication with the sample volume and configured to generate ananalyte signal that varies in response to a concentration of a targetanalyte present in the sampling volume; and a control unitcommunicatively coupled to the sampling sensor and the analyte sensor,the control unit comprising: a processor; and a computer-readable mediumstoring instructions that, when executed, cause the processor to:determine a time at which to measure the concentration of the targetanalyte in the sampling volume based on the breath signal; and at thedetermined time, measure the concentration of the target analyte in thesampling volume based on the analyte signal.
 7. The breath analytedevice of claim 6, further comprising a pump in fluid communication withthe sampling volume and configured to motivate gas from the breathvolume into the sampling volume.
 8. The breath analyte device of claim7, wherein the instructions, when executed, further cause the processorto activate the pump prior to measuring the concentration of the targetanalyte in the sampling volume.
 9. The breath analyte device of claim 7,wherein the pump is connected to the sampling volume via a pump conduitand configured to pull gas from the sampling volume.
 10. The breathanalyte device of claim 6, wherein the sampling sensor is an audiosensor.
 11. The breath analyte device of claim 10, wherein theinstructions that cause the processor to determine a time at which tomeasure the concentration of the target analyte in the sampling volumecomprise instructions that cause the processor to: detect the breathsignal increasing above a breath-detection threshold; identify a maximumin the breath signal after the breath signal increased above thebreath-detection threshold; and detect the breath signal dropping belowan end-of-breath threshold after the maximum in the breath signal,wherein the time at which to measure the concentration of the targetanalyte in the breath volume is when the breath signal drops below theend-of-breath threshold.
 12. The breath analyte device of claim 6,wherein the target analyte is acetone and the analyte sensor is anacetone sensor.
 13. The breath analyte device of claim 6, wherein theanalyte sensor is a metal-oxide sensor.
 14. The breath analyte device ofclaim 13, wherein the instructions, when executed, further cause theprocessor to prepare the sensor to measure the concentration of thetarget analyte in the sampling volume, the instructions that cause theprocessor to prepare the sensor comprising instructions that cause theprocessor to: cause the sensor to be heated to a first temperaturesufficient to burn off at least some chemicals adsorbed on an activesurface of the sensor; cause the sensor to remain at a secondtemperature sufficient to prevent significant adsorption of chemicals atthe active surface; and cause the temperature of the sensor to reduce toa third temperature, wherein the concentration of the target analyte inthe sampling volume is measured while the sensor is at the thirdtemperature.
 15. The breath analyte device of claim 14, wherein thefirst temperature is in a range from 200 C to 500 C, the secondtemperature is in a range from 150 C and 350 C, and the thirdtemperature is in a range from 200 C and 400 C.
 16. The breath analytedevice of claim 14, wherein the instructions that cause the processor toprepare the sensor further comprise instructions that cause theprocessor to: activate a pump one or more times to remove fluid from thesampling volume; and receive user input while the sensor is at thesecond temperature requesting measurement of the concentration of thetarget analyte in the sampling volume, wherein the control unit causesthe temperature of the sensor to reduce to the third temperatureresponsive to the user input.
 17. The breath analyte device of claim 6,further comprising a display, wherein the instructions further compriseinstructions that, when executed, cause the processor to instruct thedisplay to present a prompt to a user to blow into the breath volume.18. The breath analyte device of claim 17, wherein the instructionsfurther comprise instructions that, when executed, cause the processorto instruct the display to present the measured concentration of thetarget analyte to the user.
 19. The breath analyte device of claim 6,wherein the instructions that cause the processor to measure theconcentration of the target analyte in the sampling volume compriseinstructions that, when executed cause the processor to: integrate theanalyte signal over a sample period; and subtract, from the integratedanalyte signal, one or more of a baseline level or a drift correction.20. A method for preparing a sensor to measure an analyte concentration,the method comprising: heating the sensor to a first temperaturesufficient to burn off at least some chemicals adsorbed on an activesurface of the sensor; holding the sensor at a second temperaturesufficient to prevent significant adsorption of chemicals at the activesurface; receiving a signal indicating a request to measure the analyteconcentration using the sensor; and adjusting the temperature of thesensor to a third temperature, wherein the sensor is configured tomeasure the analyte concentration while the sensor is at the thirdtemperature.